tert-butyl (2R)-2-carbamothioylpyrrolidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of (R)-tert-butyl 2-carbamothioylpyrrolidine-1-carboxylate (373 mg, 1.6 mmol), 4-(bromoacetyl)pyridine.HBr (455 mg, 1.6 mmol), K2CO3 (224 mg, 1.6 mmol) and EtOH (20 mL) was heated at reflux for 4 h. The mixture was cooled and concentrated. The residues was taken up in EtOAc (90 mL), washed with 0.5 M aq NaoH (20 mL) and brine (20 mL), and dried over Na2SO4. Removal of the solvent left an amber oil (410 mg). A 379-mg portion of the crude product was purified by chromatography on a 12-g silica gel cartridge, eluted with a 0-100% EtOAc in hexanes gradient to afford (R)-tert-butyl 2-(4-(pyridin-4-yl)thiazol-2-yl)pyrrolidine-1-carboxylate (200 mg, 37%) as a tan solid. LC-MS Method 1 tR=1.20 min, m/z=332. at reflux for 4 h The mixture was cooled concentrated washed with 0.5 M aq NaoH (20 mL) and brine (20 mL) dried over Na2SO4 Removal of the solvent left an amber oil (410 mg) A 379-mg portion of the crude product was purified by chromatography on a 12-g silica gel cartridge eluted with a 0-100% EtOAc in hexanes gradient

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution Boc-D-prolinamide (2.63 g, 12.3 mmol) in CH2Cl2 (25 mL) at rt was added Lawesson's reagent (2.73 g, 6.75 mmol). The mixture was stirred overnight and concentrated. The oily residue was purified by chromatography on a 40-g silica gel cartridge, eluted with a 0-20% MeOH in CH2Cl2 gradient, to afford (R)-tert-butyl 2-carbamothioylpyrrolidine-1-carboxylate (2.65 g, 94%) as a tan solid. LC-MS Method 1 tR=1.23 min, m/z=231, 173, 131. concentrated The oily residue was purified by chromatography on a 40-g silica gel cartridge eluted with a 0-20% MeOH in CH2Cl2 gradient